ALPHA(V)BETA(3) INTEGRIN EXPRESSION IN NORMAL AND ATHEROSCLEROTIC ARTERY

Recent evidence suggests that alpha(v) beta(3) integrin is a critical molecule in several processes involved in atherosclerosis progression and in restenosis, eg, smooth muscle cell (SMC) migration and angiogenesis. While several ligands for this integrin are known to be present in atherosclerotic plaque, little is known about the presence of alpha(v) beta(3), integrin at this site. In the present study, we have examined alpha(v) beta(3) expression in normal and atherosclerotic arteries. Thirty-six coronary artery segments from the recipient hearts of 24 patients undergoing heart transplantation were classified into two groups: nonatherosclerotic diffuse intimal thickening (DIT) and atherosclerotic plaques. Serial frozen sections were examined immunohistochemically with four different monoclonal antibodies directed against human alpha(v) beta(3) complex or the beta(3) subunit and with cell markers for SMCs, macrophages, and endothelial cells. The endothelium along the lumen of both DIT and plaque arteries showed high expression of alpha(v) beta(3) The media of both DIT and plaque arteries showed less intense but extensive expression of alpha(v) beta(3) Immunoprecipitation and reverse-transcribed polymerase chain reaction (RT-PCR) analyses performed on extracts from the aortic media confirmed the presence of alpha(v) beta(3) in the media. Ln the intima of both DIT and plaque arteries, alpha,beta(3), expression generally colocalized with SMCs but rarely with macrophages. The microvessels in the adventitia as well as in the plaque showed prominent expression of alpha(v) beta(3), in contrast to low expression in similar-sized microvessels of the skin. These results suggest that alpha(v) beta(3) is present both in the normal artery and in sites of SMC accumulation and angiogenesis in atherosclerotic plaques.